Is CIDEC p.Thr49Met (c.146C>T) pathogenic?

CIDEC p.Thr49Met (c.146C>T) is classified Benign in CIDEC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-08-27). AlphaMissense: likely benign (0.1461); Low-frequency (popmax 3.79%, nfe).

How common is CIDEC p.Thr49Met (c.146C>T) in the general population?

CIDEC p.Thr49Met (c.146C>T) is low-frequency (popmax 3.79%, nfe) (gnomAD).

What do computational predictors say about CIDEC p.Thr49Met (c.146C>T)?

AlphaMissense predicts likely benign (score 0.1461) — an in-silico prediction, not a clinical call.

CIDEC p.Thr49Met

c.146C>T · rs61742367 · VCV128770

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1461 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.79%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1461	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -9.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -3.1, phastCons 0.98
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.98 · regional, not allelic
Overall
CADD	19.11	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.79% European (non-Finnish) · 43,540/1,147,310 alleles

Filtering AF 3.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.75%

Overall 3.14% 48,748/1,552,452 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	3.79%	26
Amishnot grpmax-eligible	3.52%	28
Remaining individualsnot grpmax-eligible	2.81%	36
Admixed American	2.3%	43
Middle Eastern	1.94%	51
Ashkenazi Jewishnot grpmax-eligible	1.51%	66
Finnishnot grpmax-eligible	1.17%	85
South Asian	0.715%	140
African / African-American	0.629%	159
East Asian	0.00243%	41,158

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CIDEC
Protein: p.Thr49Met
Coding: c.146C>T
MANE Select: NM_001321142
dbSNP: rs61742367
Type: single nucleotide variant
Location: chr3:9877127 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.19
Residue 49: the cide-n domain

Full CIDEC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIDEC p.Arg182His Uncertain significance ★★ ⚠ same type
CIDEC p.Ile156Thr Uncertain significance ★★ ⚠ same type
CIDEC p.Met195Ile Uncertain significance ★★ ⚠ same type
CIDEC p.Val54Met Uncertain significance ★★ ⚠ same type
CIDEC c.207+180G>A Benign ★★ same type
CIDEC c.208-91C>T Benign ★★ same type
CIDEC c.53+77T>A Benign ★★ same type
CIDEC c.-25-52G>T Benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cidec-p-thr49met (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown